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Objective: To develop and validate a radiomics-clinical combined model combining preoperative computed tomography (CT) and clinical data from patients with papillary thyroid carcinoma (PTC) to predict the efficacy of initial postoperative 131I treatment., Methods: A total of 181 patients with PTC who received total thyroidectomy and initial 131I treatment were divided into training and testing sets (7:3 ratio). Univariate analysis and multivariate logistic regression were used to screen clinical factors affecting the therapeutic response to 131I treatment and construct a clinical model. Radiomics features extracted from preoperative CT images of PTCs were dimensionally reduced through recursive feature elimination and least absolute shrinkage and selection operator. Logistic regression was used to establish a radiomics model, and a radiomics-clinical combined model was developed by integrating the clinical model. The area under the curve (AUC), sensitivity, and specificity were used to evaluate the prediction performance of each model., Results: Multivariate analysis revealed that pre-131I treatment serum thyroglobulin was an independent clinical risk factor affecting the efficacy of initial 131I treatment (P = .002), and the AUC, sensitivity, and specificity for predicting the efficacy of initial 131I treatment were 0.895, 0.899, and 0.816, respectively. After dimensionality reduction, 14 key CT radiomics features of PTCs were included. The established radiomics model predicted the efficacy of 131I treatment in the training and testing sets with AUCs of 0.825 and 0.809, sensitivities of 0.828 and 0.636, and specificities of 0.745 and 0.944, respectively. The combined model improved the AUC, sensitivity, and specificity in both sets., Conclusion: The preoperative CT-based radiomics model can effectively predict the efficacy of initial postoperative 131I treatment in patients with intermediate- or high-risk PTC, and the radiomics-clinical combined model exhibits better predictive performance., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Hyperthyroidism, caused by metastatic differentiated thyroid cancer, is a rare condition that can be difficult to diagnose. Thyrotoxicosis and metastatic disease regarding functional metastasis increase morbidity and mortality in patients with functional metastasis and need to be treated. This study aims to present a case of hyper-functional metastasis of thyroid cancer to analyze its pathological features, diagnostic procedures, and treatment options and to gather and examine recent cases of hyper-functional metastasis of thyroid cancer., Case Presentation: A 26-year-old Iranian woman presenting with hyperthyroidism and a solid cystic nodule measuring 14.5 × 15.7 × 19.6 mm in the left thyroid lobe underwent thyroid surgery revealing papillary thyroid carcinoma. Despite lymph node metastasis, she refused further surgery and opted for lymph node radiofrequency ablation and radioactive iodine therapy. Subsequent follow-ups showed no recurrence of lymphadenopathy, normalized thyroid function, and decreasing triglyceride levels, with the patient under surveillance., Conclusion: Radioactive iodine is a first-line treatment option for patients with hyperactive thyroid cancer presenting with metastatic disease. Another therapeutic option is surgery, which is performed to maximize the reduction of thyroid tissue, lymph nodes, and distant metastasis., Competing Interests: Declarations Ethics approval and consent to participate Since this study is a case report, the study did not require any ethical approval. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Accurate postoperative assessment is critical for optimizing 131 I therapy in patients with papillary thyroid cancer (PTC). This study aimed to develop a pathology model utilizing postoperative digital pathology slides to predict lymph node and/or distant metastases on post-therapeutic 131 I scan after initial 131 I treatment in PTC patients. A retrospective analysis was conducted on 229 PTC patients who underwent total or near-total thyroidectomy and subsequent 131 I treatment after levothyroxine (LT4) withdrawal between January 2022 and August 2023. The pathology model was developed through two stages: patch-level prediction and WSI-level prediction. The clinical model was constructed using statistically significant variables identified from univariate and multivariate logistic regression analysis. Of the 229 patients, 19.6% (45/229) exhibited 131 I-avid metastatic foci in post-therapeutic 131 I scan. Multifactorial analysis identified stimulated thyroglobulin (sTg) as the sole independent risk factor. The AUC of the pathology model in the training and test cohorts were 0.976 (95% CI 0.948-1.000) and 0.805 (95% CI 0.660-0.951), respectively, which were significantly higher than the clinical model (AUC 0.652 and 0.548, Pall < 0.05). This model has the potential to serve as a valuable tool for clinicians in tailoring treatment strategies, thereby optimizing therapeutic outcomes for PTC patients., (© 2024. The Author(s).)

Objectives: Differentiated thyroid cancer (DTC) is rare in the pediatric population. It remains unclear whether younger children are at greater risk of more aggressive disease. We aimed to identify prognostic factors for aggressive pediatric DTC and to define an appropriate age stratification., Methods: This retrospective cohort study included all patients aged 18 years or less who were treated for DTC between 1985 and 2021 in a tertiary medical center and were followed up for a minimum of 1.5 years after treatment., Results: Seventy-eight patients were included, all diagnosed with papillary thyroid carcinoma: 30 (38.5%) low-risk, 21 (26.9%) intermediate-risk, and 27 (34.6%) high-risk according to the American Thyroid Association (ATA) risk stratification. The mean duration of follow-up was 11.8 ± 7.8 years. No evidence of disease was documented in 52 patients (66.7%) at 1-year post-treatment and 64 patients (82.1%) at the end of follow-up. On analysis by age, evidence of disease at 1-year post-treatment was found in 66.7% of children younger than 11 years, compared to 25.4% of older children (p = 0.002). There was no significant difference by age in evidence of disease at the last follow-up (p = 0.453). Patients aged <11 years at diagnosis were associated with more aggressive disease features on histopathologic examination, metastatic disease, and high ATA risk level. Patients aged <8 years were associated with more frequent bilateral disease and extrathyroidal extension., Conclusion: Pediatric DTC patients who are younger than 11 years at diagnosis have more aggressive disease features and a lower early remission rate than older patients. Nevertheless, their long-term outcome is satisfactory., Level of Evidence: 4-retrospective cohort study Laryngoscope, 134:4818-4825, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: We aimed to compare Asian or Pacific Islander, Black, Hispanic, and non-Hispanic White patients in treatment for papillary thyroid cancer (PTC) in the equal access Military Health System to better understand racial-ethnic cancer health disparities observed in the United States., Methods: We used the MilCanEpi database to identify a cohort of men and women aged 18 or older who were diagnosed with PTC between 1998 and 2014. Low- or high-risk status was assigned using tumor size and lymph node involvement. Treatment with surgery (e.g., thyroidectomy) overall and treatment by risk status [active surveillance (low-risk) or adjuvant radioactive iodine (RAI) (high-risk)] was compared between racial-ethnic groups using multivariable logistic regression and expressed as adjusted odds ratios (AOR) with 95% confidence intervals (CIs)., Results: The study included 598 Asian, 553 Black, 340 Hispanic, and 2958 non-Hispanic White patients with PTC. Asian (AOR = 1.21, 95% CI 0.98, 1.49), Black (AOR = 1.07, 95% CI 0.87, 1.32), and Hispanic (AOR = 0.92, 95% CI 0.71, 1.19) patients were as likely as White patients to receive surgery. By risk status, there were no significant racial-ethnic differences in receipt of active surveillance or thyroidectomy for low-risk PTC or in thyroidectomy or total thyroidectomy with adjuvant RAI for high-risk PTC., Conclusions: In the Military Health System, where patients have equal access to care, there were no overall racial-ethnic differences in surgical treatment for PTC. As American Thyroid Association guidelines evolve to include more conservative treatment, further research is warranted to understand potential disparities in active surveillance and surgical management in U.S. healthcare settings., (© 2024. Society of Surgical Oncology.)

Purpose: Papillary thyroid cancer (PTC) is the most common thyroid malignancy, characterized by its slow progression and favorable prognosis. This study re-evaluates the efficacy of radioactive iodine (RAI) therapy versus no RAI in low-risk PTC patients following total thyroidectomy., Methods: A retrospective analysis was conducted on 588 patients treated between 2010 and 2016 at a major tertiary center in Turkey. Patients were divided into two cohorts: those receiving total thyroidectomy (TT) with high-dose RAI (100 mCi) and those receiving TT alone. A matched cohort of 138 patients per group was analyzed to minimize bias., Results: Follow-up data indicated that at 24 months, the RAI group demonstrated a higher percentage of excellent treatment responses (86%) compared to the non-RAI group (74%). Long-term follow-up showed that 99.3% of the RAI group achieved no evidence of disease (NED), versus 90.6% in the non-RAI group. Recurrence rates were significantly lower in the RAI group (1%) compared to the non-RAI group (5.8% with a > 2.0 ng/ml cut-off for biological events)., Conclusion: In summary, the findings from this study underscore the efficacy of RAI therapy in reducing recurrence rates and enhancing long-term disease control in low-risk papillary thyroid cancer patients. While total thyroidectomy alone is effective, the addition of RAI therapy provides a marked improvement in treatment responses and reduces the risk of disease recurrence. This indicates that personalized treatment plans incorporating RAI may offer significant advantages in managing low-risk PTC., (© 2024. The Author(s).)

Management of Localized Follicular-Derived Thyroid Cancer: The incidence of follicular-derived thyroid cancers has increased worldwide in recent decades, mainly papillary thyroid cancers at low recurrence risk. A process of de-escalation in the initial management and follow-up of these patients has therefore been implemented in parallel. This article provides the best practice recommendations made by the French learned societies (Société française d'endocrinologie, Société française de médecine nucléaire, Association française de chirurgie endocrine, Société française d'oto-rhino-laryngologie et de chirurgie de la face et du cou), european and international learned societies (European Society for Medical Oncology and the American Thyroid Association), in the management of follicular-derived thyroid cancer without distant metastases. The extent of thyroid surgery and lymph node dissection, strategies of radioiodine ablation, follow-up protocols and the management of excellent prognosis papillary cancers ≤ 10 mm will be addressed., Competing Interests: Liens d’intérêts Les auteurs déclarent ne pas avoir de liens d’intérêts. Cet article fait partie du supplément Prise en charge des cancers thyroïdiens en 2024 : avancées diagnostiques et thérapeutiques réalisé avec le soutien institutionnel de Lilly., (Copyright © 2024 Elsevier Masson SAS. Tous droits réservés. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Thyroid cancer is the most common cancer in women in Ecuador., Objective: The aim of this study was to determine the demographics and clinical and treatment variables of patients with papillary or follicular thyroid cancer, referred to as differentiated thyroid cancer (DTC), treated at a third-level hospital in Quito, Ecuador., Methods: We reviewed retrospectively the medical records of patients with DTC, who underwent surgical treatment, from 1990 to 2019. Data included demographics, pathological information, clinical stage, type of surgery, and radioactive iodine (RAI) adjuvant therapy. Patients were monitored for up to 29 years (median follow-up time 6.9 years)., Results: The corrected overall 5-, 10-, 20-, and 30-year survival rates (Kaplan-Meier) were 93%, 85%, 70%, and 63%, respectively. On univariate analysis, age, histological type, tumor grade, histological variants, capsular invasion, vascular invasion, tumor size, clinical stage, distant metastases at diagnosis, surgical margins, extrathyroidal invasion, radioactive iodine adjuvant treatment, and locoregional recurrence were found to be significant prognostic factors. In a multivariate analysis, the following independent variables: age over 55 years, extrathyroidal spread, metastasis at diagnosis, and stage II to IV raised the risk of death (hazard risk) (HR)., Conclusions: Age over 55 years, extrathyroidal spread, metastasis at diagnosis, and advanced clinical stage were found to have a harmful prognosis and an increased risk of death in a series of Ecuadorian patients surgically treated for a DTC., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Pacheco-Ojeda Luis et al.)

Objective: Differentiated thyroid cancer (DTC) is the most common pediatric endocrine cancer but studies are scarce. Latest recommendations advocate for an individualized risk-based approach to select patients for additional therapy. Lymphovascular invasion is not considered, despite being a well-known risk factor in the adult population. The aim of this study was to describe the outcomes of a cohort of DTC patients diagnosed at pediatric age and to evaluate the impact of lymphovascular invasion on the risk of persistence/recurrence., Methods: A retrospective study of patients diagnosed with DTC at pediatric age from 2010 to 2022 at a single center was performed. All patients had total thyroidectomy. Radioactive iodine therapy (RAI) was used in selected patients. The response to therapy and occurrence of persistent/recurrent disease were evaluated., Results: A total of 21 DTC were diagnosed, mostly papillary thyroid carcinoma (PTC) (81.0%, n=17). Six patients (28.6%) had nodal involvement and one (4.8%) had lung metastasis at the time of the diagnosis. Lymphovascular invasion was present in 11 patients (52.4%). After surgery, 13 patients (61.9%) underwent RAI. The mean follow-up time was 5.7±3.1 years. In total, 6 patients (31.6%) experienced persistent/recurrent disease during the follow-up time. Among PTC patients, persistent/recurrent disease was more frequent in the presence of lymphovascular invasion [55.6% (5/9) vs. 0.0% (0/6), p=0.031]., Conclusion: An individualized risk-based approach is recommended. Our study suggests that lymphovascular invasion may be associated with a higher risk of persistence/recurrence and should therefore be considered for decision making in children and adolescents with PTC., Competing Interests: Conflict of interest: None declared., (©Copyright 2024 by Turkish Society for Pediatric Endocrinology and Diabetes / The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)

Papillary thyroid cancer (PTC) is the most common type of primary thyroid cancer. Despite the low malignancy and relatively good prognosis, some PTC cases are highly aggressive and even develop refractory cancer in the thyroid. Growing evidence suggested that microenvironment in tumor affected PTC biological behavior due to different immune states. Different interconnected components in the immune system influence and participate in tumor invasion, and are closely related to PTC metastasis. Immune cells and molecules are widely distributed in PTC tissues. Their quantity and proportion vary with the host's immune status, which suggests that immunotherapy may be a very promising therapeutic modality for PTC. In this paper, we review the role of immune cells and immune checkpoints in PTC immune microenvironment based on the characteristics of the PTC tumor microenvironment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zheng, Sun and Wei.)

The prevalent histological variant within differentiated thyroid carcinoma is papillary thyroid carcinoma, also known as PTC. The study investigated the clinical performance of serum hsa&#95;circ&#95;0001955 in predicting the prognosis of PTC treated with radical thyroidectomy and iodine 131 nail clearance. The relative expression of serum circ&#95;0001955 of PTC patients was detected before and after accepting radical thyroidectomy combined with 131I thyroid remnant ablation by RT-qPCR. Serum thyroglobulin (Tg) and thyroglobulin antibody (TgAb) levels were quantified by an automatic chemiluminescence immunoassay analyzer. Multivariate logistic regression analysis was employed to investigate the risk factors associated with the prognosis of PTC patients with postoperative 131I therapy. The serum circ&#95;0001955 levels in 127 PTC patients were higher than that in 96 multinodular goiter patients and 110 healthy controls before treatment and had diagnostic values for PTC patients. After 131I treatment, serum circ&#95;0001955 levels and Tg value have a correlation with potential recurrence (WBS positive). Serum circ&#95;0001955, Tg, and TgAb value, and their combination may have diagnostic value in predicting recurrence. Serum circ&#95;0001955 levels in patients with PTC after radical thyroidectomy and iodine 131 thyroidectomy may help predict recurrence.

Purpose: Differentiated thyroid cancer (DTC) presents a complex clinical challenge, especially in patients with distant metastases and resistance to standard treatments. This study aimed to investigate the influence of specific genes and their germline single nucleotide polymorphisms (SNPs) linked to both inflammatory processes and other neoplasms on the clinical and pathological characteristics of DTC, particularly their potential impact on radioiodine (RAI) treatment efficacy., Methods: This retrospective analysis involved a cohort of 646 patients diagnosed with DTC after thyroidectomy. Study covering 1998-2014, updated in 2023, included 567 women and 79 men (median age: 49; range: 7-83). SNP selection targeted functional significance, while mutational status was assessed by pyrosequencing for comprehensive characterization. Patient genetic profiles were assessed for associations with disease characteristics, RAI response, and cancer pathology., Results: Significant correlations emerged between certain SNPs and DTC features. Notably, the NOD2 c.802 T > C variant (rs2066842) was identified as a marker distinguishing between papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). Moreover, the c.802 T allele was associated with an enhanced response to RAI treatment, indicating a more substantial decrease in posttreatment stimulated thyroglobulin (sTg) concentrations. The NFKB1A allele c.126A (rs696) exhibited connections with lower FTC stages and a reduced probability of multifocality., Conclusion: This study explored the molecular mechanisms of particular SNPs, highlighting the role of NOD2 in innate immunity and the stress response, and its potential impact on RAI efficacy. This research underscores the clinical promise of SNP analysis and contributes to personalized treatment strategies for DTC, emphasizing the relevance of genetic factors in cancer progression and treatment outcomes., (© 2024. The Author(s).)

Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid cancer (THCA) and shows a better prognosis than other types. However, further research is needed to determine the risk of PTC. We herein used the CIBERSORT algorithm to analyze the gene-expression profile obtained from TCGA, estimated the infiltration ratio of 22 immune cell types in tumor tissues and normal tissues, analyzed the differential expression of immune-related genes, and identified immune cells and immune-related genes related to clinical progress and prognosis. We uncovered 12 immune cell types and nine immune-related genes that were closely correlated with TNM staging, and two immune cell types (activated NK cells and γδT cells) and one immune-related gene (CD40LG) that were associated with prognosis. After evaluation, four immune cell types could be used to determine low-risk PTC, with six immune cell types and six immune-related genes closely associated with high-risk PTC. The type and quantity of infiltrating immune cells in the microenvironment of PTC, as well as immune-related genes, appear to be closely related to tumor progression and can therefore be used as important indicators for the evaluation of patient prognosis. We posit that the study of immune cells and immune-related genes in the tumor microenvironment will facilitate the determination of low-risk PTC more accurately, and that this will greatly promote the development of high-risk PTC immunotherapy., (© 2024. The Author(s).)

Background: Current management options for PTMC include lobo-isthmectomy and active surveillance (AS). Recently, ultrasound-guided minimally invasive procedures (MITs) are offered as a nonsurgical therapy for PTMC because they do not require hospitalization and general anaesthesia, and do not result in loss of thyroid function or cosmetic damage. MITs are reported to consistently provide, mostly in large retrospective series of patients, a rapid, safe, and cost-effective way to eradicate low-risk thyroid malignancies. However, conclusive data from well-conducted prospective studies on the histologically-proven completeness of tumor ablation and the long-term clinical advantages versus AS are still lacking., Objectives: This study aimed to evaluate the efficacy and safety of ultrasound-guided minimally invasive treatments (MITs) for PTMC in comparison to traditional surgical methods and active surveillance, and to assess their role in current clinical practice., Methods: A structured literature review was conducted using keywords related to PTMC, MIT, and comparative techniques. Studies were evaluated based on treatment modality, patient selection, follow-up duration, complication rates, and clinical outcomes., Results: MITs have shown promising results in the management of PTMC. These treatments offer several advantages over surgery, such as reduced use of surgical resources, lower costs, minimal work disruption, and fewer major complications. However, there are still limitations, including the need for long-term surveillance and the potential risk of incomplete tumor ablation., Conclusions: MITs represent a promising non-surgical option for managing low-risk PTMC, especially for patients ineligible for or refusing surgery. Despite favorable outcomes, more robust prospective data are needed to confirm their long-term benefits and completeness of tumor ablation. Interdisciplinary discussions and thorough patient education on the advantages and limitations of MITs are crucial for informed decision-making., (© 2024. The Author(s).)

Thyroid cancer is the most common endocrine malignancy. With increasing imaging utilization, there has been an increase in the recognition of small, indolent cancers that would otherwise go undiagnosed. Historically, the surgical recommendation for all patients with thyroid cancer was a total thyroidectomy. However, over the last 20 years, there have been numerous studies evaluating the de-escalation of interventions for low-risk thyroid cancers, transitioning from total thyroidectomy to thyroid lobectomy or active surveillance when indicated. Here, we review the current literature and recommendations with each of these treatment options., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mesenchymal stem-cell-derived extracellular vesicles (MSC-EVs) have been increasingly investigated for cancer therapy and drug delivery, and they offer an advanced cell-free therapeutic option. However, their overall effects and efficacy depend on various factors, including the MSC source and cargo content. In this study, we isolated EVs from the conditioned medium of human immature dental pulp stem cells (hIDPSC-EVs) and investigated their effects on two papillary thyroid cancer (PTC) cell lines (BCPAP and TPC1). We observed efficient uptake of hIDPSC-EVs by both PTC cell lines, with a notable impact on gene regulation, particularly in the Wnt signaling pathway in BCPAP cells. However, no significant effects on cell proliferation were observed. Conversely, hIDPSC-EVs significantly reduced the invasive capacity of both PTC cell lines after 120 h of treatment. These in vitro findings suggest the therapeutic potential of hIDPSC-EVs in cancer management and emphasize the need for further research to develop novel and effective treatment strategies. Furthermore, the successful internalization of hIDPSC-EVs by PTC cell lines underscores their potential use as nanocarriers for anti-cancer agents.

Background: Lymph node metastasis is the major cause of increased recurrence and death in patients with papillary thyroid carcinoma (PTC). We evaluate the clinicopathologic factors affecting excellent response (ER) in patients with PTC with lymph node metastasis following operation and 131 I ablation therapy., Methods: A total of 423 patients with PTC with lymph node metastasis who underwent thyroidectomy and postoperative 131 I ablation therapy were enrolled. The relationship between clinicopathological factors affecting ER achievement was analyzed., Results: Multivariate analysis showed that the foci diameter (≤1 cm), unifocal, combination with Hashimoto's thyroiditis (HT), lymph node metastases rate (LR) (≤40%), no postoperative lymph node metastasis, low preablative stimulated thyroglobulin (ps-Tg) level (≤3.87 ng/mL), and the time of 131 I ablation therapy (one time) were positively correlated with the ER achievement [odds ratio (OR): 1.744, 3.114, 3.920, 4.018, 2.074, 9.767, and 49.491, respectively; all p < 0.05]. The receiver operating characteristic (ROC) curves showed that the cutoff values of ps-Tg and LR were 4.625 ng/mL and 50.50%, respectively. The AUC of ROC of ps-Tg and LR for predicting ER achievement was 0.821 and 0.746, respectively. The Tg and the cumulative risk of non-ER elevated with the increase of LR, especially for the high-level ps-Tg (>4.625 ng/mL) group., Conclusion: The foci diameter and number, combination with HT, LR, and ps-Tg level are independent factors for ER. Ps-Tg level and LR are valid predictive factors for the efficacy of 131 I therapy in patients with PTC. The predictive value of the cumulative risk of non-ER can be improved by the combination of ps-Tg and LR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Li, Yu, Wang, Guo, Ni, Zhao, Wang and Dong.)

Background and Purpose: Thyroid papillary carcinoma (PTC) had a high possibility of recurrence after surgery, and thyroid stimulating hormone (TSH) suppression and radioactive iodine ( 131 I) were used for postoperative therapy. This study explored the potential mechanism of lymph node metastasis (LNM) and aimed to develop differentiated treatments for PTC., Method: This study explored the risk factors of lymph node metastasis in PTC by analyzing the clinical information of 2073 cases. The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) and the Gene Expression Omnibus (GEO) databases of gene expression were analyzed to identify the interrelationships between gene expression to phenotype., Results: Analyzing clinical data, we found that male gender, younger age, larger tumor size, and extra-thyroidal extension (ETE) were risk significant risk factors for lymph node metastasis(P<0.05). Conversely, thyroid function parameters such as TSH, FT3, FT4, TSH/FT3, and TSH/FT4 didn't correlate with LNM(P>0.05), and TSH levels were observed to be higher in females(P<0.05). Gene expression analysis revealed that SLC5A5 was down-regulated in males, younger individuals, and those with lymph node metastasis, and a lower level of SLC5A5 was associated with a worse disease-free survival(P<0.05). Additionally, our examination of single-cell RNA sequencing (scRNA-seq) data indicated that SLC5A5 expression was reduced in tumors and lymph node metastasis samples, correlating positively with the expression of TSHR., Conclusion: The impact of TSH on PTC behavior remained unclear, while the capacity for absorbing 131 I in dependence on SLC5A5 showed variations across different genders and ages. We conclude that postoperative treatment of PTC should take into account the differences caused by gender and age., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yan, Sun, He and Jia.)

Although most differentiated thyroid carcinoma has a clinically favorable prognosis, some of specific types of thyroid cancer (such as anaplastic thyroid carcinoma and advanced papillary thyroid carcinoma) show fatal outcomes and require novel treatments. Immunotherapy is a promising avenue for the treatment of advanced thyroid carcinoma. B7-H3 (B7 homolog 3 protein) and ICAM-1 (intercellular adhesion molecule 1), as two important immune checkpoints (ICPs), is becoming hopeful target spots for immunotherapy. A growing amount of evidence has suggested that B7-H3 and ICAM-1 are upregulated in papillary thyroid carcinoma. However, their expression level in specific types of thyroid cancer remains largely unclear. In the present study, we explored the expression level of B7-H3 and ICAM-1 in different types of thyroid carcinoma. In the groups of the TCGA cohort, both B7-H3 and ICAM-1 mRNA were highly expressed in thyroid carcinoma. Furthermore, the patients with Stage2, 61-80y, Follicular thyroid papillary carcinoma and N0 had lower B7-H3 and ICAM-1 mRNA expression. In the groups of our cohort, PTCs and ATCs showed frequently moderate to strong expression of B7-H3 and ICAM-1 protein expression. The significant relevance of B7-H3 staining score with ICAM-1 staining score was observed in TCGA database and our cohort, which might open avenues for the combination therapy in advanced thyroid cancer., (© 2024. The Author(s).)

Objectives: Thyroid cancer rarely occurs in children and adolescents. Molecular markers such as BRAF , RAS , and RET/PTC have been widely used in adult PTC. It is currently unclear whether these molecular markers have equivalent potential for application in pediatric patients. This study aims to explore the potential utility of a multi-gene conjoint analysis based on next-generation targeted sequencing for pediatric papillary thyroid carcinoma (PTC)., Materials and Methods: The patients diagnosed with PTC (aged 18 years or younger) in the pediatrics department of Lishui District Hospital of Traditional Chinese Medicine were retrospectively screened. A targeted enrichment and sequencing analysis of 116 genes associated with thyroid cancer was performed on paraffin-embedded tumor tissues and paired paracancerous tissue of fifteen children (average age 14.60) and nine adults (average age 49.33) PTC patients. Demographic information, clinical indicators, ultrasonic imaging information and pathological data were collected. The Kendall correlation test was used to establish a correlation between molecular variations and clinical characteristics in pediatric patients., Results: A sample of 15 pediatric PTCs revealed a detection rate of 73.33% (11/15) for driver gene mutations BRAF V600E and RET fusion. Compared to adult PTCs, the genetic mutation landscape of pediatric PTCs was more complex. Six mutant genes overlap between the two groups, and an additional seventeen unique mutant genes were identified only in pediatric PTCs. There was only one unique mutant gene in adult PTCs. The tumor diameter of pediatric PTCs tended to be less than 4cm (p<0.001), and the number of lymph node metastases was more than five (p<0.001). Mutations in specific genes unique to pediatric PTCs may contribute to the onset and progression of the disease by adversely affecting hormone synthesis, secretion, and action mechanisms, as well as the functioning of thyroid hormone signaling pathways. But, additional experiments are required to validate this hypothesis., Conclusion: BRAF V600E mutation and RET fusion are involved in the occurrence and development of adolescent PTC. For pediatric thyroid nodules that cannot be determined as benign or malignant by fine needle aspiration biopsy, multiple gene combination testing can provide a reference for personalized diagnosis and treatment by clinical physicians., Competing Interests: Authors NY, XL and YX were employed by the company Dian Diagnostics Group Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Wang, Tan, Wu, Wang, Tan, Du, Li, Xu, Yan and Qian.)

Background: Lymph node metastases in papillary thyroid cancer (PTC) increase the risk for persistent and recurrent disease. Data on the predictive value of histopathological features of lymph node metastases, however, are inconsistent. The aim of this study was to evaluate the prognostic significance of known and new histopathological features of lymph node metastases in a well-defined cohort of PTC patients with clinically evident lymph node metastases., Methods: A total of 1042 lymph node metastases, derived from 129 PTC patients, were reexamined according to a predefined protocol and evaluated for diameter, extranodal extension, cystic changes, necrosis, calcifications, and the proportion of the lymph node taken up by tumor cells. Predictors for a failure to achieve a complete biochemical and structural response to treatment were determined., Results: The presence of more than 5 lymph node metastases was the only independent predictor for a failure to achieve a complete response to treatment (odds ratio [OR] 3.39 [95% CI, 1.57-7.33], P < .05). Diameter nor any of the other evaluated lymph node features were significantly associated with the response to treatment., Conclusions: Detailed reexamination of lymph nodes revealed that only the presence of more than 5 lymph node metastases was an independent predictor of failure to achieve a complete response to treatment. No predictive value was found for other histopathological features, including the diameter of the lymph node metastases. These findings have the potential to improve risk stratification in patients with PTC and clinically evident lymph node metastases., Competing Interests: Conflict of interest: W.E.V. is on the editorial board of EJE. He was not involved in the review or editorial process for this paper, on which he is listed as author. The other authors have no conflict of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.)

Purpose of Review: The aim of this study was to provide a timely and relevant review of the latest findings and explore appropriate management of aggressive variants of papillary thyroid cancer (AVPTC)., Recent Findings: In general, AVPTCs tend to exhibit more invasive characteristics, a lack of responsiveness to radioiodine, increased occurrences of regional spreading, distant metastases and higher mortality rates. Meanwhile, each variant showcases unique clinical and molecular profiles., Summary: Given the elevated risk of recurrence postsurgery, a more aggressive strategy may be necessary when suspected preoperatively, particularly for those presenting with invasive features. Decision on the extent of surgical treatment and adjuvant therapy is individualized and made by experienced clinicians and multidisciplinary teams based on the clinical presentation, presence of aggressive features and molecular profile. Future studies on development of personalized medicine and molecular target therapy may offer tailored treatment options., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Both anaplastic thyroid cancer (ATC) and papillary thyroid cancer (PTC) originate from thyroid follicular epithelial cells, but ATC has a significantly worse prognosis and shows resistance to conventional therapies. However, clinical trials found that immunotherapy works better in ATC than late-stage PTC. Here, we used single-cell RNA sequencing (scRNA-Seq) to generate a single-cell atlas of thyroid cancer. Differences in ATC and PTC tumor microenvironment components (including malignant cells, stromal cells, and immune cells) leading to the polarized prognoses were identified. Intriguingly, we found that CXCL13+ T lymphocytes were enriched in ATC samples and might promote the development of early tertiary lymphoid structure (TLS). Last, murine experiments and scRNA-Seq analysis of a treated patient's tumor demonstrated that famitinib plus anti-PD-1 antibody could advance TLS in thyroid cancer. We displayed the cellular landscape of ATC and PTC, finding that CXCL13+ T cells and early TLS might make ATC more sensitive to immunotherapy.

Background: The American Thyroid Association (ATA) recurrence risk prediction system considers vascular invasion (VI) as a relative indicator for adjuvant radioactive iodine (RAI) treatment, nevertheless VI final role in PTC management is yet to be defined. This study aims to assess the impact of histologic VI in papillary thyroid carcinoma (PTC)., Methods: A retrospective study with PTC patients admitted in our Thyroid Cancer Unit, between January 1960 and December 2016 was performed. We reviewed 905 patient records with 275 having full information about VI on their pathological reports. Demographic and clinical variables were obtained, and univariate/multivariate analysis was performed in order to obtain potential predictive prognostic factors., Results: Fifty-one out 275 patients presented VI (18.5%; 95% CI 14.4-23.6%), these individuals had larger tumors (median 19 mm vs. 12 mm, P<0.001) with more frequent extraglandular invasion (54.0% vs. 17.1%, P<0.001), regional lymph nodes involvement (29.8% vs. 12.6%, P=0.003)and distant metastasis (10.9% vs. 1.9%, P=0.003) at diagnosis. VI was an independent predictor for regional lymph node and/or distant metastasis at diagnosis (OR 2.93 [IC 95% 1.16-7.41, P=0.008]). After a median follow-up time was 68.5 months patients with VI presented higher rates of local recurrence and lymph node metastasis recurrence., Conclusions: In this study, the presence of VI in PTC is associated to higher rate of lymph node and distant metastasis at diagnosis. Its presence should be probably considered an adverse prognostic factor in PTC, perhaps justifying more aggressive therapeutic and follow-up approaches in such cases.

Background: Few studies have examined the disparities in access to care for pediatric thyroid cancers. We sought to clarify socioeconomic and patient factors that affect access to care for pediatric differentiated thyroid cancer and aggressive variants of papillary thyroid cancer., Methods: Using the National Cancer Database, we performed a retrospective study on pediatric differentiated thyroid cancer and aggressive variants of papillary thyroid cancer (2004-2019). Patients were divided into three periods (2004-2008, 2009-2013, 2014-2019) to assess for trends. The χ 2 analysis and Kruskal-Wallis test were used to test for independence of groupings for each socioeconomic and disease-related factor., Results: In all, 6,275 patients with pediatric differentiated thyroid cancer and 182 with aggressive variants of papillary thyroid cancer were analyzed. Differentiated thyroid cancer patients with Medicaid (median 18.0 miles) and those from lower-income households (median 21-30 miles) had to travel greater distances for care in recent years (2014-2019). Racial/ethnic disparities were evident; Black and Hispanic patients have higher odds of waiting >30 days for surgery (odds ratio 1.39, 1.49, P < .05, respectively) than White patients. Black patients with differentiated thyroid cancer had a higher risk of mortality compared with White and Hispanic patients (hazard ratio 4.31, 95% confidence interval: 1.95-9.51, P < .05). Nodal positivity was higher in Hispanic patients with differentiated thyroid cancer (60%, P < .05, White patients 51% and Black patients 36%). Socioeconomic factors did not significantly affect survival or nodal positivity in aggressive variants of papillary thyroid cancer., Conclusion: This study highlights disparities in access to care and survival outcomes in pediatric differentiated thyroid cancer and aggressive variants of papillary thyroid cancer. Race, income status, and type of insurance all play a role in these disparities. Understanding the complex etiologies and developing interventions to improve access and patient outcomes are crucial., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The 2015 American Thyroid Association guidelines proposed recurrence risk stratification of differentiated thyroid carcinoma, including papillary thyroid carcinoma (PTC), but this stratification excluded non-initial treatment patients with worse outcomes. This study aimed to explore the potential risk factors for recurrence in PTC and develop a predictive model for both initial and non-initial treatment of patients with PTC., Methods: A total of 955 patients were included in this study. Differences between the recurrence (-) and recurrence (+) groups were compared. The 955 patients were randomized into two groups: the training group (671 cases) and the validation group (284 cases). All variables were selected using the LASSO regression analysis. A nomogram was developed based on the results of the univariate and multivariate logistic regression analyses. The nomogram performance was evaluated using discrimination and calibration., Results: Patients aged ≥55 years, extranodal extension (ENE), metastatic LN ratio (LNR) >0.5, and non-initial treatment were identified as potential risk factors for recurrence through LASSO regression and univariate and multivariate analyses. The receiver operating characteristic curve (ROC curve) showed high efficiency, with an area under the ROC curve (AUC) of 0.819 (95% confidence interval [CI], 0.729-0.909) and 0.818 (95% CI, 0.670-0.909) in the training and validation groups, respectively. The calibration curve indicated that the nomogram had a good consistency., Conclusion: In patients with PTC, age ≥55 years, ENE, LNR >0.5, and non-initial treatment are potential risk factors for recurrence. The predictive model of recurrence was confirmed to be a practical and convenient tool for clinicians to accurately predict PTC recurrence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Tian, Jiang, Wang, Gao, Wei, Yang and Li.)

Background: Papillary thyroid cancer (PTC) is the most common endocrine malignancy worldwide. The treatment of PTC has attracted extensive attention and discussion from the public and scholars. However, no article has systematically assessed the related literature. Therefore, we conducted a bibliometric and knowledge map analysis to reveal the dynamic scientific developments in the PTC therapy field., Methods: We retrieved publications related to PTC therapy from the Web of Scientific Core Collection (WoSCC) on May 1, 2023. The bibliometric package in R software, VOSviewer and CiteSpace software were used to analyze countries/regions, institutions, journals, authors, references, and keywords. Then, we systematized and summarized the research landscape, global trends and hot topics of research., Results: This bibliometric analysis spanned from 2012 to 2022 and involved 18,501 authors affiliated with 3,426 institutions across 87 countries/regions, resulting in the publication of 3,954 papers in 860 academic journals. Notably, the number of publications and citations related to PTC therapy research has exhibited a steady increase over the past decade. China and the United States have emerged as leading contributors in terms of publication count, with the United States also being the most cited country. Furthermore, among the top 10 institutions with the highest number of published papers, half were located in China. Among the journals, Thyroid is ranked first in terms of total publications and citations. The most productive individual author was Miyauchi Akira. While previous research primarily focused on surgery and radioactive iodine therapy, the increasing emphasis on health awareness and advancements in medical technology have led to the emergence of active surveillance, thermal ablation, and genomic analysis as prominent areas of research., Conclusion: In conclusion, this comprehensive and quantitative bibliometric analysis elucidates the research trends and hotspots within PTC therapy, drawing from a substantial body of publications. This study provides valuable insights into the historical and current landscape of PTC therapy research while also offering guidance for future research directions. This study serves as a valuable resource for researchers and practitioners seeking new avenues of exploration in the field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Song, Lin, Feng, Zhao and Teng.)

Background: Internationally, several clinical practice guidelines recommend active surveillance as a nonsurgical management strategy for select patients with low-risk papillary thyroid carcinoma. However, patient's decision making when choosing active surveillance as a management approach is not well understood. Thus, our aim was to examine the barriers and facilitators to selecting active surveillance among patients with low-risk papillary thyroid carcinoma in China. Methods: Thirty-nine participants diagnosed with low-risk papillary thyroid carcinoma were purposively recruited between July and November 2021 for semistructured interviews; 24 of whom rejected and 15 patients chose "active surveillance" as a management approach in our sample. Inductive content analysis illustrated emerging themes. Audit trails, member checks, and thematic discussions were used to assert rigor. Results: Barriers and facilitators were classified as patient-related, disease-related, and external factors. Patient-related factors included patient's knowledge, attitudes, and emotions. Disease-related factors included the response to having cancer, the constant state of being diseased, and perceived value of the thyroid gland. External factors included the residual effects of surgery, the active surveillance protocol, and physicians' recommendations. Conclusions: Patient's acceptability of the active surveillance as a management approach are complex with many influencing factors. The public acceptance of active surveillance as a disease management approach needs to be improved, through the presentation of active surveillance as an evidence-based and optimized dynamic management strategy. Clinicians must address their patients' psychological struggles when patients choose active surveillance and patients require more attention and supportive intervention.

The pathogenesis and treatment of papillary thyroid cancer with desmoid-type fibromatosis (PTC-DTF), a rare subtype of papillary thyroid carcinoma characterized by a mixed epithelial-mesenchymal structure, are still ill-defined. Previous reports on PTC-DTF have had limited follow-up and recurrence has been rarely reported. To better understand this condition, we conducted a thorough analysis of five cases of PTC-DTF from our institute, including clinical and pathological examinations, imaging, immunohistochemistry, and molecular analysis. We also reviewed relevant literature. The mean age of the patients was 51.8 years, with three women and two men included in the group. Ultrasound often showed a hypoechogenic and well-defined nodule in the thyroid gland, except for one individual who had distant lung metastases detected by PET-CT. The nodules ranged in width from 0.5 to 5.0 cm and were excised in each case. Following surgery, 131 I therapy was used in two cases. The overall number of PTC-DTF cases has risen from the previously reported 55 to 60, with females being the most commonly affected and ranging in age from 19 to 82. Most masses underwent a thyroidectomy, and approximately half of the patients had lymph node metastases. Histologically, PTC-DTFs were composed of a predominant stromal component (65%-90%) and an intervening epithelial component. These spindle cells were arranged in parallel with abundant cytoplasm and vacuole-like nucleus but there wasn't evident atypia. The carcinoma cells were positively stained for CK and TTF-1 by immunohistochemistry, whereas mesenchymal cells were positive for SMA and displayed nuclear immunoreactivity for β-catenin. BRAF, NRAS, and CTNNB1 mutations were identified in the epithelial and mesenchymal components through molecular testing, respectively. Perhaps because the mesenchyme harbors aberrant nuclear β-catenin expression, PTC-DTF is more aggressive and prone to invasion and distant recurrence, as shown by our case 2, which is the first case to be reported thus far. PTC-DTF is typically treated with surgery, but clinicians may occasionally consider more holistic treatment plans that involve radioactive iodine and endocrine therapy., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: While the impact of insurance has been described for thyroid cancer as a whole, we sought to further characterize this relationship for the papillary sub-group (PTC)., Methods: Those patients with primary site thyroid tumors from 2007 to 2016 with histology-confirmed PTC were extracted from the SEER database. These parameters yielded 103 219 participants for demographic, extent of disease, and treatment parameter study and 103 025 for outcome studies., Results: Compared to their counterparts, those with Medicaid were more likely to have stage T3 or greater (<.0001) disease at presentation. Those with Medicare/private insurance were more likely to have No staging at diagnosis ( P  < .0001). Similarly, those with Medicaid exhibited poorer overall (98.0%, 90.9%, 81.6% vs 98.9%, 95.0%, 90.0%; P  < .0001) and cause-specific (99.3%, 98.0%, 95.8% vs 99.7%, 99.1%, 98.4%; P  < .0001) survival after 1, 5, and 9 years respectively., Conclusion: Insurer has a significant impact on the stage at diagnosis of papillary thyroid carcinoma while having limited effect on the treatment modalities offered. Statistically significant overall and cause-specific mortality differences were appreciated but are likely clinical insignificant. Further work to elucidate the social factors likely affecting these patients is warranted.

Objective: We assessed the contribution of initial treatment response to further refining prediction of individual outcomes in intermediate-risk papillary thyroid cancer (PTC) on the American Thyroid Association (ATA) risk stratification system. Dynamic risk stratification (DRS) as originally proposed by Tuttle et al. in 2010 was modified to also include serum antithyroglobulin antibodies (TgAb) as a surrogate marker of the likelihood of persistent disease, specifically in patients with thyroglobulin assay interference by TgAb., Methods: Three hundred and seventy-three patients with ATA intermediate-risk PTC were enrolled retrospectively upon reviewing medical records. Patients were followed at the National Cancer Institute in Bogota, Colombia after being treated with total thyroidectomy and I-131 therapy between 2009 and 2013. Best response to initial therapy was classified as excellent, indeterminate, biochemically incomplete or structurally incomplete. Final disease status after a median follow-up of 7.1 years was classified as no evidence of disease (NED), indeterminate, or persistent disease (either biochemically or structurally). The rate of recurrence was determined in excellent responders., Results: Excellent response was achieved by 164 patients (43.9%). At a median follow-up of 42 months, 19 (11.6%) had experienced recurrence. 87.4% of initially excellent responders available at the final checkpoint were NED, compared to 28% of those with biochemically or structurally incomplete response and to 60.2% of all ATA intermediate-risk PTC patients in our cohort., Conclusions: Modified DRS further predicted individual outcomes in intermediate-risk PTC, potentially allowing ongoing management to be tailored accordingly., (Copyright © 2022. Published by Elsevier Masson SAS.)

The incidence of differentiated thyroid cancer (DTC) has been increasing worldwide, mostly, as an increase in the incidental detection of micro papillary thyroid carcinomas (microPTCs), many of which are potentially overtreated, as suggested by the unchanged mortality. Several international guidelines have suggested a less aggressive approach. More recently, it has been shown that active surveillance or minimally invasive treatments (MIT) are good alternatives for the management of these patients. In this context, patient participation in the decision-making process is paramount. The Endocrine Task Force of the European Organisation for Research and Treatment of Cancer (EORTC) has undertaken the task to establish consensus and define its position based on the scientific evidence concerning, 1) the current state of diagnostic and management options in microPTCs, including the current opinion of physicians about shared decision making (SDM), 2) the available evidence concerning patients' needs and the available decision instruments, and 3) to provide practical suggestions for implementation of SDM in this context. To improve SDM and patients' participation, knowledge gaps and research directions were highlighted., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: Over time, the American Thyroid Association (ATA) guidelines have increasingly promoted more limited treatments for well-differentiated thyroid cancers., Objective: To determine whether the 2009 and 2015 ATA guidelines were associated with changes in the management of low-risk papillary thyroid carcinomas on a national scale., Design, Setting, and Participants: This historical cohort study used the National Cancer Database. All papillary thyroid carcinomas diagnosed from 2004 to 2019 in the National Cancer Database were selected. Patients with tumors of greater than 4 cm, metastases, or clinical evidence of nodal disease were excluded. Data were analyzed from August 1, 2021, to September 1, 2022., Main Outcomes and Measures: The primary aim was to tabulate changes in the rates of thyroid lobectomy (TL), total thyroidectomy (TT), and TT plus radioactive iodine (RAI) therapy after the 2009 and 2015 ATA guidelines. The secondary aim was to determine in which settings (eg, academic vs community) the practice patterns changed the most., Results: A total of 194 254 patients (155 796 [80.2%] female patients; median [range] age at diagnosis, 51 [18-90] years) who underwent treatment during the study period were identified. Among patients who underwent surgery, rates of TL decreased from 15.1% to 13.7% after the 2009 guidelines but subsequently increased to 22.9% after the 2015 changes. Among patients undergoing TT, rates of adjuvant RAI decreased from 48.7% to 37.1% after 2009 and to 19.3% after the 2015 guidelines. Trends were similar for subgroups based on sex and race and ethnicity. However, academic institutions saw larger increases in TL rates (14.9% to 25.7%) than community hospitals (16.3% to 19.5%). Additionally, greater increases in TL rates were observed for tumors 1 to 2 cm (6.8% to 18.9%) and 2 to 4 cm (6.6% to 16.0%) than tumors less than 1 cm (22.8% to 29.2%)., Conclusions and Relevance: In this cohort study among patients with papillary thyroid carcinomas up to 4 cm, ATA guideline changes corresponded with increased TL and reduced adjuvant RAI. These changes were primarily seen in academic institutions, suggesting an opportunity to expand guideline-based care in the community setting.

Objective: Thyroid carcinoma (TC) is the most common endocrine tumor in the human body. Papillary thyroid carcinoma (PTC) accounts for more than 80% of thyroid cancers. Accurate prediction of elderly PTC can help reduce the mortality of patients. We aimed to construct a nomogram predicting cancer-specific survival (CSS) in elderly patients with PTC., Methods: Patient information was downloaded from the Surveillance, Epidemiology, and End Results (SEER) program. Univariate and multivariate Cox regression models were used to screen the independent risk factors for patients with PTC. The nomogram of elderly patients with PTC was constructed based on the multivariate Cox regression model. We used the concordance index (C-index), the area under the receiver operating characteristic curve (AUC) and the calibration curve to test the accuracy and discrimination of the prediction model. Decision curve analysis (DCA) was used to test the clinical value of the model., Results: A total of 14,138 elderly patients with PTC were included in this study. Patients from 2004 to 2015 were randomly divided into a training set (N = 7379) and a validation set (N = 3141), and data from 2016 to 2018 were divided into an external validation set (N = 3618). Proportional sub-distribution hazard model showed that age, sex, tumor size, histological grade, TNM stage, surgery and chemotherapy were independent risk factors for prognosis. In the training set, validation set and external validation set, the C-index was 0.87(95%CI: 0.852-0.888), 0.891(95%CI: 0.866-0.916) and 0.931(95%CI:0.894-0.968), respectively, indicating that the nomogram had good discrimination. Calibration curves and AUC suggest that the prediction model has good discrimination and accuracy., Conclusions: We constructed a new nomogram to predict CSS in elderly patients with PTC. Internal cross-validation and external validation indicate that the model has good discrimination and accuracy. The predictive model can help doctors and patients make clinical decisions., (© 2022. The Author(s).)

The incidence of differentiated thyroid carcinoma (DTC) has increased in recent decades with early stage, low risk papillary thyroid cancer (PTC) being detected and diagnosed. As a result, the psychological, financial, and clinical ramifications of overdiagnosis and excessively aggressive therapy are being increasingly recognized with many authorities calling for a re-evaluation of the traditional "one size fits all" management approaches. To address these critical issues, most thyroid cancer guidelines endorse a more risk adapted management strategy where the intensity of therapy and follow up is matched to the anticipated risk of recurrence and death from DTC for each patient. This "less is more" strategy provides for a minimalistic management approach for properly selected patients with low-risk DTC. This has re-kindled the long-standing debate regarding the routine use of radioactive iodine therapy (RIT) in DTC. Although recent guidelines have moved toward a more selective use of RIT, particular in patients with low-intermediate risk DTC, the proper selection of patients, the expected benefit, and the potential risks continue to be a source of ongoing controversy and debate. In this manuscript, we will review the wide range of clinical, imaging, medical team, and patient factors that must be considered when evaluating individual patients for RIT. Through a review of the current literature evaluating the potential benefits and risks of RIT, we will present a risk adapted approach to proper patient selection for RIT which emphasizes peri-operative risk stratification as the primary tool that clinicians should use to guide initial RIT management recommendations.

As a traditional treatment for papillary thyroid cancer (PTC), surgical resection of diseased tissues often brings lots of inconveniences to patients, and the tumor recurrence and metastasis are difficult to avoid. Herein, we developed a gene and photothermal combined therapy nanosystem based on a polypyrrole (Ppy)-poly(ethylene imine)-siILK nanocomplex (PPR ILK ) to achieve minimally invasive ablation and lymphatic metastasis inhibition in PTC simultaneously. In this system, gelatin-stabilized Ppy mainly acted as a photothermal- and photoacoustic (PA)-responsive nanomaterial and contributed to its well-behaved photosensitivity in the near-infrared region. Moreover, gelatin-stabilized Ppy possessed a charge reversal function, facilitating the tight conjunction of siILK gene at physiological pH (7.35-7.45) and its automatic release into acidic lysosomes (pH 4.0-5.5); the proton sponge effect generated during this process further facilitated the escape of siILK from lysosomes to the cytoplasm and played its role in inhibiting PTC proliferation and lymphatic metastasis. With the guidance of fluorescence and PA bimodal imaging, gene delivery and Ppy location in tumor regions could be clearly observed. As a result, tumors were completely eradicated by photothermal therapy, and the recurrences and metastases were obviously restrained by siILK.

Papillary thyroid carcinoma (PTC) with hobnail areas above 30% is classified as hobnail variant (HVPTC). Although it is widely accepted that HVPTC has a worse outcome than classical PTC, it is unclear whether PTC with hobnail features below 30% is as aggressive as HVPTC. We gathered the largest mono-institutional series of PTC with hobnail areas and HVPTC to evaluate differences in terms of pathological features of aggressiveness, molecular profile, and treatment outcome. A total of 99 PTC with hobnail features above 5% were retrospectively selected; 34 of them met the criteria for HVPTC (0.4% of all PTC diagnosed at our institution). All tumors showed high rates of extra-thyroidal extension (40.4%), lymph node metastasis (68.1% of patients with lymphadenectomy), and vascular emboli (49.5%), with no differences according to the 30% cutoff. On the other hand, distant metastases were present in HVPTC only (9.4%). Also, advanced age, advanced disease stage, and TERT promoter mutation were associated with HVPTC. More than half of the patients with follow-up had structural or biochemical persistence after 1 year from surgery. Structural persistence was significantly more common in patients with HVPTC (37.5% vs. 8.7%), while no differences were observed considering structural and biochemical persistence together. The presence of hobnail features identifies locally aggressive tumors, and, consequently, it should be always acknowledged in the pathological report. However, tumors with more than 30% hobnail areas frequently present TERT promoter mutations, advanced disease stage, and structural persistence after radioiodine ablation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Poma, Macerola, Proietti, Vignali, Sparavelli, Torregrossa, Matrone, Basolo, Elisei, Santini and Ugolini.)

Thyroid cancer (TC) is the eighth most frequently diagnosed cancer worldwide with a rising incidence in the past 20 years. Surgery is the primary strategy of therapy for patients with medullary TC (MTC) and differentiated TC (DTC). In DTC patients, radioactive iodine (RAI) is administered after thyroidectomy. Neck ultrasound, basal and thyroid-stimulating hormone-stimulated thyroglobulin are generally performed every three to six months for the first year, with subsequent intervals depending on initial risk assessment, for the detection of possible persistent/recurrent disease during the follow up. Distant metastases are present at the diagnosis in ∼5 % of DTC patients; up to 15 % of patients have recurrences during the follow up, with a survival reduction (70 %-50 %) at 10-year. During tumor progression, the iodide uptake capability of DTC cancer cells can be lost, making them refractory to RAI, with a negative impact on the prognosis. Significant advances have been done recently in our understanding of the molecular pathways implicated in the progression of TCs. Several drugs have been developed, which inhibit signaling kinases or oncogenic kinases (BRAF V600E , RET/PTC), such as those associated with Platelet-Derived Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor. Tyrosine kinase receptors are involved in cancer cell proliferation, angiogenesis, and lymphangiogenesis. Several tyrosine kinase inhibitors (TKIs) are emerging as new treatments for DTC, MTC and anaplastic TC (ATC), and can induce a clinical response and stabilize the disease. Lenvatinib and sorafenib reached the approval for RAI-refractory DTC, whereas cabozantinib and vandetanib for MTC. These TKIs extend median progression-free survival, but do not increase the overall survival. Severe side effects and drug resistance can develop in TC patients treated with TKIs. Additional studies are needed to identify a potential effective targeted therapy for aggressive TCs, according to their molecular characterization., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Spinal metastases (SpMs) from thyroid cancers (TC) significantly reduce quality of life by causing pain, neurological deficits in addition to increasing mortality. Moreover, prognosis factors including surgery remain debated., Methods: Data were stored in a prospective French national multicenter database of patients treated for SpM between January 2014 and 2017. Fifty-one consecutive patients affected by TC with 173 secondary SpM were included., Results: Mean overall survival (OS) time for all patients from the diagnosis of a thyroid SpM event was 9.1 years (SD 8.7 months). The 1-year, 5-year and 10-year survival estimates were 94% (SD 3.3), 83.8.0% (SD 5.2), and 74.5% (SD 9.9). The median period of time between primary thyroid tumor diagnosis and the SpM event was 31.4 months (SD 71.6). In univariate analysis, good ECOG-PS (status 0 and 1) (p < 0.0001), ambulatory status (Frankel score) (p < 0.0001) and no epidural involvement (p = 0.01), were associated with longer survival, whereas cancer subtype (p = 0.436) and spine surgery showed no association (p = 0.937). Cox multivariate proportional hazard model only identified good ECOG-PS: 0 [HR: 0.3, 95% CI 0.1-0.941; p < 0.0001], 1 [HR: 0.8, 95% CI 0.04-2.124; p = 0.001] and ambulatory neurological status: Frankel E [HR: 0.262, 95% CI 0.048-1.443; p = 0.02] to be independent predictors of better survival., Conclusion: For cases presenting SpM from TC, we highlighted that the only prognostic factors were the progression of the cancer (ECOG-PS) and the clinical neurological impact of the SpM (Frankel status). Surgery should be discussed mainly for stabilization and neurological decompression., Competing Interests: Declaration of competing interest The authors declare that they have no personal conflicts of interest and no institutional financial interest in any drugs, materials, or devices described in this manuscript. The authors have no financial disclosures to report. In addition, all patients gave their informed consent for any medical and scientific investigations. This paper has not been published previously, is not under consideration for publication elsewhere. All authors are responsible for reported research., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: We examine whether surgery extent and radiation administration affect overall survival for cT2N0M0 classic papillary thyroid cancer according to age and sex., Methods: Patients with cT2N0M0 classic papillary thyroid cancer tumors in the National Cancer Data Base (2004-2016) were selected. Multivariable Cox regression analysis compared patients (combined male + female cohorts) having lobectomy to those having total thyroidectomy with or without radiation (primarily radioactive iodine) for ages: 18 to 45, 46 to 55, and >55 years. In addition, 1:1 propensity score matching and Kaplan-Meier curves with 10-year overall survival estimates, and log-rank test were stratified by age and sex., Results: Lobectomy had equivalent overall survival to total thyroidectomy without and with radiation for patients (combined male + female cohorts) aged 18 to 45 and 46 to 55 years on multivariable analysis. On propensity score matching there was overall survival advantage for total thyroidectomy with radiation over both lobectomy and total thyroidectomy for men (ages 18-90+ combined) and overall survival advantage in patients (combined male + female cohort) aged >55 years having total thyroidectomy with radiation versus lobectomy. On propensity score matching there were no overall survival differences in women (ages 18-90+ combined) or patients (combined male + female cohort) aged 18 to 45 and 46 to 55 years having either lobectomy, total thyroidectomy, or total thyroidectomy with radiation., Conclusion: For cT2N0M0 classic papillary thyroid cancer, total thyroidectomy with radiation improves 10-year overall survival for patients (combined male + female cohort) aged >55 years and men (ages 18-90+ combined)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The discovery of RNA interference (RNAi) has opened a new strategy in cancer therapy, especially by silencing target genes. Pharmacologically it can be achieved by introducing of small (19-21 base pairs) dsRNA molecules known as small interfering RNA (siRNA) targeting interested genes. siRNA mediated gene has been widely investigated for its utility in treating various diseases including cancer. However, the systemic delivery of interested siRNA via non-viral methods remains a major challenge with large numbers of polymeric and liposomal systems being tested. The most effective methods involving cationic liposomes delivery to cells. Nonetheless, systemic delivery of siRNA via cationic lipid particles is often poor due to rapid uptake by reticuloendothelial organs, resulting in decreased delivery of these particles to the site of interest. Polyethylene glycol (PEG) has been used in siRNA-liposomes formulation to minimize reticuloendothelial uptake. Also, PEGylation permits the accumulation of the liposomes-loaded siRNA at the tumor sites with defective vasculatures such as enhanced permeability and retention phenomena. Thus, a simple method to prepare stable PEGylated siRNA-loaded lipid particles could provide better systemic delivery system in treating various cancers, including papillary thyroid carcinoma. Here we illustrate a simple protocol for the formulation of siRNA-loaded lipid particles by hydration of freeze-dried matrix (HFDM) method for effective delivery of target specific siRNA to papillary thyroid carcinoma cells., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Tall cell variant of papillary thyroid carcinoma is an aggressive subtype of papillary thyroid carcinoma. We examined expression of cancer stem cell markers in tall cell variant compared with other well-differentiated thyroid cancers., Methods: Expression of cancer stem cell markers was examined in 572 thyroid tumors from The Cancer Genome Atlas Thyroid Cancer database and tall cell variant and papillary thyroid carcinoma tumors by immunohistochemistry., Results: Expression of the PROM1 gene, encoding the cancer stem cell marker CD133, was elevated in tall cell variant compared to classic papillary thyroid carcinoma in a large cohort of unmatched samples from The Cancer Genome Atlas Thyroid Cancer database (P < .001). By immunohistochemistry in age and stage matched samples, CD133 protein was confirmed to be significantly increased in tall cell variant versus classic papillary thyroid carcinoma (P = .006). Analyzing all thyroid cancers, high PROM1 expression was associated with worse disease-specific survival. Optimal cutoffs were determined to define a tall cell variant-like cancer stem cell signature characterized by high PROM1, high ALDH1A3, and low CD24 expression. Classic papillary thyroid carcinoma with a tall cell variant-like gene signature had worse recurrence disease-free survival compared to classic papillary thyroid carcinoma with a non-tall cell variant signature (P = .02)., Conclusion: Tall cell variant of papillary thyroid carcinoma has increased expression of cancer stem cell markers compared to classic papillary thyroid carcinoma. The tall cell variant-like cancer stem cell gene signature identified a molecular subtype of classic papillary thyroid carcinoma that has a worse recurrence-free survival., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: An ongoing debate exists over the optimal management of low-risk papillary thyroid cancer. The American Thyroid Association supports the concept of active surveillance to manage low-risk papillary thyroid cancer; however, the cost-effectiveness of active surveillance has not yet been established. We sought to perform a cost-effectiveness analysis comparing active surveillance versus surgical intervention for patients in the United States., Methods: A Markov decision tree model was developed to compare active surveillance and thyroid lobectomy. Our reference case is a 40-year-old female who was diagnosed with unifocal (<15 mm), low-risk papillary thyroid cancer. Probabilistic outcomes, costs, and health utilities were determined using an extensive literature review. The willingness-to-pay threshold was set at $50,000/quality-adjusted life year gained. Sensitivity analyses were performed to account for uncertainty in the model's variables., Results: Lobectomy provided a final effectiveness of 21.7/quality-adjusted life years, compared with 17.3/quality-adjusted life years for active surveillance. Furthermore, incremental cost effectiveness ratio for lobectomy versus active surveillance was $19,560/quality-adjusted life year (

Background: Multidisciplinary Tumor Boards (MDT) are used to obtain input regarding cancer management. This study assessed the impact of our institutional Endocrine MDT., Methods: MDT notes on patients with thyroid cancer treated during 2012-2018 were abstracted retrospectively from the electronic medical record. Management change (MC) was prospectively collected by the MDT coordinator. Biannual evaluations reviewed the impact of the MDT as observed by attendees., Results: MC was recommended in 47 (15%) of 286 presentations, with additional imaging being the most frequent (43%). Presentation of recurrences were more likely to result in MC (24% vs. 13% initial, p = 0.03). Overall, 98% of attendees found the conference exceeded educational expectations. About 24% reported intending to use a more evidence/guideline-based approach after attending and this trend increased over time (p = 0.002)., Conclusion: MDT presentations led to a higher rate of MC particularly in recurrent TC patients and increased evidenced-based practice for attendees., (Copyright © 2021. Published by Elsevier Inc.)